BALTIMORE – Sen. Barbara Mikulski, a tough and dogged daughter of working-class Baltimore who rose to become the longest-serving woman in the history of Congress, said she had one question as she weighed seeking a sixth term: “Do I spend my time raising money, or do I spend my time raising hell?”

The 78-year-old Maryland Democrat, who led the powerful Appropriations Committee, announced Monday that she’d decided on the latter approach and would not seek...